PROJECT SUMMARY Chronic aspiration is a life-threatening survivorship issue, afflicting up to 30% of patients treated with curative radiotherapy for head and neck cancers. Aspirators are almost 5-times more likely to develop pneumonia than non-aspirators, and pneumonia confers a 42% increased risk of mortality among head and neck cancer survivors. While swallowing therapies modestly impact on quality-of-life (QOL), there is still no effective treatment to reverse chronic radiation-associated aspiration. Earlier identification of at-risk populations and refined therapies are needed. The long-term goal of this work is to prevent dysphagia-related pneumonia after head and neck radiotherapy through incorporation of strategies designed to monitor and adapt therapy through quantitative imaging of functional kinetics and swallowing motion in head and neck tissues. We expect novel spatial metrics will provide capacity for image-guided radiation therapy, impacting tumor control and toxicity simultaneously. The effort is well positioned to generate independent, substantive applications for radiation planning as well as rehabilitation and outcome measurement. The objective of the proposed studies is to implement advanced magnetic resonance imaging (MRI) to monitor structure-function relationships in swallowing regions-of-interest (ROI) during and after head and neck radiotherapy. Our central hypothesis is that MRI parameters can identify subclinical dysphagia and facilitate individualized image-guided margin reduction in radiation planning. In this application, we propose to conduct swallowing optimization studies in patients enrolled on 2 extramurally funded parent prospective trials with serial MRI acquisition. In this R01 application, we propose leveraging data collected from parent trials including swallowing MRI sequences and fluoroscopy protocols with the specific aims: 1) validate the utility of candidate imaging biomarkers of neuromuscular swallowing injury (dysphagia) induced by head and neck radiotherapy, and 2) reduce radiation planning margins through MRI-guided quantification of multi-ROI swallowing motion and resultant dose- dependent dysphagia. We also plan to develop an open source access DICOM library for MRI, fluoroscopy, and clinical dysphagia characterization.